Project Summary Tissues contain multiple cell types (nerve, vasculature, epithelium, fibroblasts) that enable their specialized physiological functions. Quantitative molecular analysis of cells from histological slides is useful in developing a deeper understanding of fundamental pathophysiology and in generating effective clinical interventions. Several strategies were developed in the past to more precisely recover cells from heterogeneous tissue sections, including manual razor scrapes, micromanipulators, and laser microdissection technologies. Laser dissection in particular has become an effective and established method, with several companies now offering high-level instrumentation and accompanying microgenomics assays. However, laser dissection instruments alone are not sufficient to fully meet the needs of the molecular pathology and biology fields. We recently invented a micropurification technology that can recover specific cells or subcellular structures from histology slides within minutes and with extreme precision. If successfully optimized and validated, the invention will expand the repertoire of tools available to the research, molecular pathology and oncology communities, and enable experiments requiring a level of precision that no current technology can accomplish. The two specific aims are: Aim 1 ? Optimization of Cell and Nuclear Enrichment Aim 2 ? Advancement of mRNA and miRNA Analyses